Pulmonary alveolar macrophages (PAM) and pulmonary interstitial macrophages (PIM) play important roles in the removal of insoluble or pathogenic particulate matter from the lung. Although common oxidant pollutants, such as nitrogen dioxide (NO2) and ozone (O3) may injure macrophages and impair their effectiveness in particle clearance, the mechanism(s) for cellular injury has not been clearly established. Because past attempts to describe the in vivo toxicology of oxidants on lung macrophages have been encumbered by the dynamic nature of cell turnover within the lung, the correlation of responses to a specific, exposed population of cells has not been successful. Therefore, it is the aim of this proposal to incorporate and in vitro exposure system and directly expose isolated PAM and PIM to NO2 and O3. The proposed in vitro studies will create and exposure situation resembling in vivo conditions and help clarify the mechanism(s) for NO2- and O3-mediated injury. In vitro exposures of PAM and PIM will be conducted at various oxidant concentrations, and functional, morphological and biochemical parameters of macrophage activities will be monitored to establish the mode and dose-dependency for adverse effects. These studies will compare the sensitivity to oxidants and elucidate the roles of PAM and PIM, a phagocytic cell which replaces PAM damaged or killed by oxidants, in lung clearance.